CAR T-cell therapy represents a groundbreaking approach to harnessing the power of the body's immune system to combat cancer. By modifying T cells, a subset of white blood cells, in a laboratory setting, these cells are empowered to recognize and eliminate cancer cells with precision. Often categorized as a form of cell-based gene therapy, CAR T-cell therapy involves altering the genetic makeup of T cells, equipping them with the ability to target specific cancer antigens.
This innovative treatment has demonstrated remarkable efficacy, particularly in cases where conventional therapies have proven ineffective. Its ability to reprogram the immune system to target and destroy cancer cells marks a significant advancement in cancer treatment strategies.
Classification:
CAR T cell therapy is classified as follows:
- Structure-based classification:
- First-generation CAR T-cells: These CAR T-cells typically consist of an antigen-binding domain (single-chain variable fragment, scFv) linked to a T-cell activation domain, such as the CD3ζ chain. They lack additional co-stimulatory domains.
- Second-generation CAR T-cells: These CAR T-cells include an additional co-stimulatory domain, such as CD28 or 4-1BB (CD137), along with the CD3ζ chain. The presence of co-stimulatory domains enhances T-cell activation and persistence.
- Third-generation CAR T-cells: These CAR T-cells incorporate two co-stimulatory domains along with the CD3ζ chain, aiming to further enhance T-cell function and anti-tumor activity.
Antigen-based classification: It includes
- CD19-targeted CAR T-cells: CD19 is a common target for CAR T-cell therapy and is used in the treatment of B-cell malignancies such as acute lymphoblastic leukemia (ALL) and certain types of lymphoma.
- Other antigen-targeted CAR T-cells: CAR T-cells can be engineered to target a variety of antigens expressed on cancer cells, including but not limited to BCMA (B-cell maturation antigen), CD22, CD30, and EGFRvIII.
Before undergoing CAR T-cell therapy, patients may experience various signs and symptoms related to their underlying cancer and overall health. These symptoms can vary depending on the type and stage of cancer, as well as individual factors. Here are some common signs and symptoms that patients may experience before CAR T-cell therapy:
- Fatigue, unexplained weight loss, fever, night sweats, persistent cough, changes in bowel or bladder habits, and persistent pain or discomfort.
- patients with leukemia may experience symptoms such as easy bruising or bleeding, frequent infections, and bone pain. Patients with lymphoma may have enlarged lymph nodes, fever, and night sweats.
- Patients may present with symptoms of advanced or metastatic cancer, such as jaundice (yellowing of the skin and eyes), difficulty breathing, neurological symptoms, or abdominal pain.
- Patients may also experience symptoms related to their overall health, such as fatigue, weakness, nausea, vomiting, loss of appetite, and changes in mood or mental status.
- Patients who have undergone prior cancer treatments such as chemotherapy, radiation therapy, or surgery may experience side effects or complications from these treatments, such as hair loss, nausea, neuropathy, or surgical wounds.
Following are the diagnoses and tests used to perform:
ete Blood Count (CBC): This assesses the levels of different types of blood cells, including red blood cells, white blood cells, and platelets. Changes in these levels can indicate potential complications such as cytopenias.
Cytokine Levels: Measurement of cytokine levels in the blood can help diagnose cytokine release syndrome (CRS), a common complication of CAR T-cell therapy. Elevated levels of cytokines such as interleukin-6 (IL-6) are often associated with CRS.
Blood Chemistry Panel: This test evaluates the levels of various chemicals in the blood, including electrolytes, kidney function markers (e.g., creatinine), and liver function markers (e.g., liver enzymes). Abnormalities in these can indicate potential complications such as tumor lysis syndrome (TLS) or organ dysfunction.
Imaging Studies: Imaging tests such as computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, or positron emission tomography (PET) scans may be used to assess the size and extent of tumors before and after CAR T-cell therapy. These tests help evaluate the treatment's effectiveness and detect potential complications such as tumor growth or inflammation.
Flow Cytometry: It is a technique used to analyze the characteristics of cells, including their surface markers and intracellular components. It can be used to assess the presence and activity of CAR T-cells in the patient's bloodstream and monitor their expansion and persistence over time.
Biopsy: A tissue biopsy may sometimes be performed to obtain a tumor tissue sample for further analysis. Biopsy samples can be examined under a microscope or subjected to molecular testing to assess the response to CAR T-cell therapy and detect any changes in the tumor's genetic profile.
After the infusion, the patient must stay in the hospital for a few weeks. The doctor monitors the efficacy of CAR T-cell therapy and its side effects. Even after the discharge, there are chances that the patient may be re-admitted due to complications. The patient should visit the hospital for a follow-up that may last for months. During the long-term recovery, the patient may have tests, such as blood tests, physical examinations, and imaging tests.
Hendrik van Daniel Rheede
India
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